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Identifier 000447550
Title Μελέτη δεικτών ανοσοπαράλυσης στους ασθενείς με covid-19 λοίμωξη στη μονάδα εντατικής θεραπείας και συσχέτιση με την έκβαση
Alternative Title Study of immunoparalysis markers in covid-19 critically ill patients at ICU and correlation with outcome
Author Τσερλικάκης, Νικόλαος-Μιχαήλ
Thesis advisor Βαπορίδη, Αικατερίνη
Reviewer Κονδύλη, Ευμορφία
Νότας, Γεώργιος
Abstract Introduction In critically ill patients with sepsis, or other life-threatening illness or trauma, the acute phase is followed by generalized immune dysfunction, often referred to as severe immunosuppression or immunoparalysis. This immunoparalysis results in susceptibility to nosocomial infections, which is the leading cause of morbidity and mortality in intensive care units. The pathogenesis of immunoparalysis is not known, while the need to find diagnostic and therapeutic means is imperative. Patients with Covid-19 disease are a group of patients of particular interest in whom the presence of immunoparalysis has not yet been fully studied. Monocytes / macrophages are central mediators of natural immunity. Contributing to the identification of pathogens, antigen presentation, and the destruction of microorganisms, macrophages are the main regulators of the inflammatory response. Signs of macrophage dysfunction have been described in critically ill patients, such as decreased cytokine production and decreased HLA receptor expression, and have been associated with adverse patient outcome. Monocyte function has not been studied in Covid-19 long-term ICU patients. Objective The aim of the study was to investigate the presence of immunoparalysis in patients treated with Covid-19 disease in the ICU after the 5th day of admission, as manifested by decreased TNFa production after stimulation with lipopolysaccharide and increased concentration of interleukin-10. This study examined two questions: (1) the length of stay of Covid-19 patients in the ICU to determine the risk of nosocomial infections (2) the presence of immunoparalysis in patients treated with Covid-19 disease in the ICU after the 5th day of hospitalization, as manifested by reduced TNFα production after stimulation with lipopolysaccharide and increased interleukin concentration 10. Methodology The study included adult patients treated in the intensive care unit of the University Hospital of Heraklion with Sars-CoV-19 infection. Demographics as well as data on disease course, medication, infection and patient outcome are obtained from the patient's medical record. Approval is obtained from patients or their legal representatives to participate in the study. In a blood sample taken on the 5th-7th day of the patients' hospitalization, the appearance of immunoparalysis will be examined, as this is indicated by the reduced production of cytokines in the blood after stimulation with lipopolysaccharide. Specifically, the patients blood sample will be incubated for 4 hours with lipopolysaccharide at 37 degrees, after centrifuge the serum is separated from whole blood and stored for analysis. The cytokine concentrations will be compared the stimulated and non-stimulated sample. The absence of increased cytokine production will be considered as an indicator of immunoparalysis. Results The age distribution of Sars-CoV 2 positive patients that were finally studied is from 41-88 years with a mean value of 70 years and a standard deviation of 12.5 , 58.33% were men and 41.66% women, while in the healthy group 85.71% were women and 14.28% men. The mean stay of patients in the ICU was 27.5 days and only 50% 12 patients were discharged from the ICU. In addition, 83.33% of patients developed a health care-related infection (HAI) and of these patients 17/20 (85%) developed VAP and 3/20 (15%) developed CRBSI. During the study, patients had a secondary infection which we divided into two categories depending on the day of onset of the infection after sampling. The first category is the patients who developed an infection before 5 days of sampling in the ICU and make up 80% (16/20) while in the remaining patients 20% (4/20) developed an infection after the 5th day after sampling. Conclusions Measuring immune function in critically ill patients with Sars-CoV 2 infection and correlating patient-centered outcomes is a necessity. Within the limitations of this study, we found that, firstly, nosocomial infections are very common and important for the outcome of severely ill patients with Sars-CoV 2 infection and secondly, most (90%) of these patients develop dysfunction of the immune system, as assessed by measuring interleukin 10 and TNFα production following an ex-vivo LPS challenge test, which may be associated with nosocomial infections. However, further study is needed to evaluate the ability of this assay to quantify immune function during a critical illness and the usefulness of other biomarkers in characterizing immune dysfunction.
Language Greek
Subject ΜΕΘ
Issue date 2022-03-30
Collection   School/Department--School of Medicine--Department of Medicine--Post-graduate theses
  Type of Work--Post-graduate theses
Permanent Link https://elocus.lib.uoc.gr//dlib/d/b/d/metadata-dlib-1650359379-339854-27523.tkl Bookmark and Share
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